6g4z - Revision history

OCA at 06:37, 22 August 2018

OCA — Wed, 22 Aug 2018 06:37:46 GMT

←Older revision		Revision as of 06:37, 22 August 2018
Line 1:		Line 1:

-	==Crystal structure of ~~human~~ NF-kappaB inducing kinase (NIK) in complex with compound 2f==	+	==Crystal structure of murine NF-kappaB inducing kinase (NIK) in complex with compound 2f==
	<StructureSection load='6g4z' size='340' side='right' caption='[[6g4z]], [[Resolution\|resolution]] 2.84Å' scene=''>		<StructureSection load='6g4z' size='340' side='right' caption='[[6g4z]], [[Resolution\|resolution]] 2.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==

OCA at 19:11, 1 August 2018

OCA — Wed, 01 Aug 2018 19:11:08 GMT

←Older revision		Revision as of 19:11, 1 August 2018
Line 3:		Line 3:
	<StructureSection load='6g4z' size='340' side='right' caption='[[6g4z]], [[Resolution\|resolution]] 2.84Å' scene=''>		<StructureSection load='6g4z' size='340' side='right' caption='[[6g4z]], [[Resolution\|resolution]] 2.84Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[6g4z]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G4Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G4Z FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[6g4z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G4Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G4Z FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ELW:5-fluoranyl-1-[4-[2-[(3~{R})-1-methyl-3-oxidanyl-2-oxidanylidene-pyrrol-3-yl]ethynyl]pyridin-2-yl]indazole-3-carboxamide'>ELW</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ELW:5-fluoranyl-1-[4-[2-[(3~{R})-1-methyl-3-oxidanyl-2-oxidanylidene-pyrrol-3-yl]ethynyl]pyridin-2-yl]indazole-3-carboxamide'>ELW</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Map3k14, Nik ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></td></tr>		<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></td></tr>
	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6g4z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g4z OCA], [http://pdbe.org/6g4z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g4z RCSB], [http://www.ebi.ac.uk/pdbsum/6g4z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g4z ProSAT]</span></td></tr>		<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6g4z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g4z OCA], [http://pdbe.org/6g4z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g4z RCSB], [http://www.ebi.ac.uk/pdbsum/6g4z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g4z ProSAT]</span></td></tr>
Line 23:		Line 24:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Lk3 transgenic mice]]
	[[Category: Mitogen-activated protein kinase kinase kinase]]		[[Category: Mitogen-activated protein kinase kinase kinase]]
	[[Category: Hymowitz, S G]]		[[Category: Hymowitz, S G]]

OCA at 07:21, 4 July 2018

OCA — Wed, 04 Jul 2018 07:21:03 GMT

←Older revision		Revision as of 07:21, 4 July 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 6g4z is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of human NF-kappaB inducing kinase (NIK) in complex with compound 2f==
		+	<StructureSection load='6g4z' size='340' side='right' caption='[[6g4z]], [[Resolution\|resolution]] 2.84Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[6g4z]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6G4Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6G4Z FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ELW:5-fluoranyl-1-[4-[2-[(3~{R})-1-methyl-3-oxidanyl-2-oxidanylidene-pyrrol-3-yl]ethynyl]pyridin-2-yl]indazole-3-carboxamide'>ELW</scene></td></tr>
		+	<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Mitogen-activated_protein_kinase_kinase_kinase Mitogen-activated protein kinase kinase kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.25 2.7.11.25] </span></td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6g4z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6g4z OCA], [http://pdbe.org/6g4z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6g4z RCSB], [http://www.ebi.ac.uk/pdbsum/6g4z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6g4z ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/M3K14_MOUSE M3K14_MOUSE]] Lymphotoxin beta-activated kinase which seems to be exclusively involved in the activation of NF-kappa-B and its transcriptional activity. Promotes proteolytic processing of NFKB2/P100, which leads to activation of NF-kappa-B via the non-canonical pathway. Could act in a receptor-selective manner.<ref>PMID:11239468</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	NF-kappaB-inducing kinase (NIK) is a protein kinase central to the non-canonical NF-kappaB pathway downstream from multiple TNF receptor family members, including BAFF, which have been associated with B cell survival and maturation, dendritic cell activation, secondary lymphoid organ development, and bone metabolism. We report herein the discovery of a lead chemical series of NIK-inhibitors that was identified through a scaffold-hopping strategy using structure-based design. Electronic and steric properties of lead compounds were modified to address glutathione conjugation and amide hydrolysis. These highly potent compounds exhibited selective inhibition of LTbetaR-dependent p52 translocation and transcription of NF-kappaB2 related genes. Compound 4f is shown to have a favorable pharmacokinetic profile across species and to inhibit BAFF-induced B cell survival in vitro and reduce splenic marginal zone B cells in vivo.

-	~~Authors~~:	+	A scaffold-hopping approach to discover potent, selective and efficacious inhibitors of NF-kappaB inducing kinase.,Blaquiere N, Castanedo G, Burch J, Berezhkovskiy L, Brightbill H, Brown S, Chan C, Chiang PC, Crawford JJ, Dong T, Fan P, Feng J, Ghilardi N, Godemann R, Gogol E, Grabbe A, Hole A, Hu B, Hymowitz SG, Alaoui Ismaili MH, Le H, Lee P, Lee W, Lin X, Liu N, McEwan P, McKenzie B, Silvestre H, Suto E, Sujathabhaskar S, Wu G, Wu LC, Zhang Y, Staben ST J Med Chem. 2018 Jun 25. doi: 10.1021/acs.jmedchem.8b00678. PMID:29940120<ref>PMID:29940120</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 6g4z" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Mitogen-activated protein kinase kinase kinase]]
		+	[[Category: Hymowitz, S G]]
		+	[[Category: Leonardo-Silvestre, H]]
		+	[[Category: McEwan, P A]]
		+	[[Category: Map3k14]]
		+	[[Category: Nf-kappab]]
		+	[[Category: Protein serine/threonine kinase]]
		+	[[Category: Transferase]]

OCA at 06:51, 2 May 2018

OCA — Wed, 02 May 2018 06:51:02 GMT

←Older revision		Revision as of 06:51, 2 May 2018
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 6g4z is ON HOLD	+	The entry 6g4z is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "6g4z" [edit=sysop:move=sysop]

OCA — Wed, 04 Apr 2018 04:53:56 GMT

Protected "6g4z" [edit=sysop:move=sysop]

←Older revision

Revision as of 04:53, 4 April 2018

OCA: New page: '''Unreleased structure''' The entry 6g4z is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 04 Apr 2018 04:53:55 GMT

New page: '''Unreleased structure''' The entry 6g4z is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 6g4z is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]